A phase 3 trial of Sanofi’s eczema prospect amlitelimab has hit its primary and key secondary endpoints. Yet, with the data falling short of analyst expectations, shares in the company opened down 9% in Paris.
The trial tested amlitelimab, an anti-OX40L antibody that Sanofi has predicted could generate peak sales in excess of $5 billion. Based on phase 2 results, TD Cowen analysts said in a note to investors earlier this week that their base case phase 3 readout was a 45% to 50% rate of EASI-75 and a 35% to 40% rate of IGA0/1 after 24 weeks of monthly dosing.
Thursday, Sanofi reported EASI-75 of 35.9% and 46%, depending on which patients were included. The drugmaker also reported validated investigator global assessment scale for atopic dermatitis (vIGA-AD) 0/1 of 21.1% and 26.5%, again depending on which patients were included.
EASI-75 looks at the proportion of patients reaching a 75% or greater improvement in the eczema area and severity index total score. Sanofi used the vIGA-AD to look at the proportion of patients with clear or almost clear skin.
The results were statistically significant compared to placebo, achieving the co-primary endpoints of the trial. However, the response rates fell into TD Cowen analysts’ bear case scenario. In that scenario, the analysts predicted Sanofi’s stock would slump below 80 euros ($93). Investors sent the stock down to 78.36 euros in early morning trading in Paris.
Meanwhile on the Nasdaq, Sanofi was down more than 7% when trading opened Wednesday morning.
In a note to clients posted Wednesday morning, analysts at Jefferies said that Sanofi's drug "doesn't replicate [phase 2] efficacy and looks soft compared to other biologics. However, the drug clearly works at dosing every 12 weeks with efficacy improving over time and is safe. Middle of the pack on efficacy with best convenience should still be a drug."
Analysts at Leerink said in its breakdown of the data that: "Despite the underwhelming efficacy, it is possible that amlitelimab could find a role in [second line] settings, particularly given the novel mechanism of action and convenience of Q12W dosing. But the atopic dermatitis landscape is set to become increasingly crowded over the next several years, likely with novel drugs with better efficacy than amlitelimab."
Cross-trial comparisons are complicated by the lack of equivalent 24-week data on Eli Lilly’s Ebglyss and Sanofi and Regeneron’s Dupixent. The phase 3 Dupixent program delivered (PDF) EASI-75 rates of 44% to 69% after 16 weeks across three studies.
Amgen has also struggled to convince analysts that its OX40 drug candidate rocatinlimab can compete, despite the company racking up phase 3 wins. After seeing phase 3 data, TD Cowen analysts wrote that the antibody “showed good efficacy and better than expected tolerability, although unlikely to unseat Dupixent and will likely face stiff competition from [Sanofi’s] amlitelimab.”
The extent to which amlitelimab is a threat to rocatinlimab—and vice versa—will become clearer across a series of data drops. Amgen is scheduled to publish data from two phase 3 trials by the end of the year. Sanofi expects to share results from the four other phase 3 trials in its Oceana clinical development program through 2026.
TD Cowen analysts said the readouts are “mission critical” for Sanofi. Amlitelimab is important to Sanofi “not only because of its peak sales potential, but perhaps, more importantly, for sentiment around [its] R&D efforts,” the analysts said.
Sentiment soured in May when Sanofi reported the failure of a phase 3 trial of its Regeneron-partnered IL-33 drug candidate itepekimab in chronic obstructive pulmonary disease. In recent months, Sanofi has also reported the failure of phase 2 trials of an oral TNF inhibitor in psoriasis and amlitelimab in asthma.